The reciprocal relationship between the gut microbiota and its human host is extremely complex. The dynamic changes that occur in gut microbiota in response to its host physiological state and the influence it has on human physiology are poorly understood. Evidence has suggested that the gut microbiota can influence glucose metabolism. Despite these findings, the role of the microbiota in the onset and development of type 2 diabetes mellitus (T2D) has yet to be fully understood. We propose to apply an omics-centric approach in which many genes, proteins, metabolites and cytokines comprising functional pathways in both the host and the microbiome are interrogated for quantitative changes associated with the onset and development of T2D. Through longitudinal in-depth profiling of the host and the microbiota, we will identify molecular and biochemical signatures for the host and the microbiota associated with the development of T2D. The integration and temporal profiles of these data will provide an unprecedented view of the global host-microbiota changes that occur during the transition to T2D.